Cardiac Fas-dependent and mitochondria-dependent apoptosis in ovariectomized rats.
BACKGROUND
Very limited information has been published regarding cardiac apoptosis in menopausal women or in those after bilateral oophorectomy. The purpose of this study was to evaluate whether cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways are activated in ovariectomized rats.


METHODS
Thirty-two female Wistar rats at 6-7 months of age were randomly divided into sham-operated group (Sham) and bilateral ovariectomized group (OVX). Two months after the operation, the cardiac characteristics, myocardial architecture, and two major apoptotic pathways in the excised left ventricle from rats were measured by histopathological analysis, Western blotting and reverse transcription polymerase chain reaction (RT-PCR), and positive TUNEL assays.


RESULTS
The whole heart weight, the left ventricular weight, the ratios of whole heart weight to tibia length, and the ratios of left ventricle to tibia length were significantly increased in OVX relative to Sham. Abnormal myocardial architecture, enlarged interstitial spaces, more minor cardiac fibrosis, and more cardiac TUNEL-positive apoptotic cells were observed in OVX. The key components of Fas-dependent apoptosis (TNF-alpha, Fas ligand, Fas death receptors, Fas-associated death domain (FADD), activated caspase 8, and activated caspase 3) and key components of mitochondria-dependent apoptosis (Bad, Bax, Bax-to-Bcl2 ratio, cytosolic cytochrome c, activated caspase 9, and activated caspase 3) were significantly increased in OVX hearts.


CONCLUSIONS
The absence of female ovaries will activate the cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which might provide one of possible mechanism for developing heart failure in post-menopause women.
Lee
Shin-Da
SD
Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan.
Kuo
Wei-Wen
WW
Ho
Ying-Jui
YJ
Lin
Ann-Chi
AC
Tsai
Chang-Hai
CH
Wang
Hsueh-Fang
HF
Kuo
Chia-Hua
CH
Yang
Ai-Lun
AL
Huang
Chih-Yang
CY
Hwang
Jin-Ming
JM
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001835:Body Weight; D005260:Female; D008593:Menopause / Q000502:physiology*; D008929:Mitochondria, Heart / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D009929:Organ Size; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology*
D019014:fas Receptor